Dealing with uncertainty: turbulent parameterizations and grid-spacing effects in numerical modelling of deep moist convective processes

Abstract. Computer power has grown to the point that very-fine-mesh mesoscale modelling is now possible. Going down through scales is clumsily supposed to reduce uncertainty and to improve the predictive ability of the models. This work provides a contribution to understand how the uncertainty in the numerical weather prediction (NWP) of severe weather events is affected by increasing the model grid resolution and by choosing a parameterization which is able to represent turbulent processes at such finer scales. A deep moist convective scenario, a supercell, in a simplified atmospheric setting is studied by mean of high resolution numerical simulations with COSMO-Model. Different turbulent closures are used and their impacts on the space-time properties of convective fields are discussed. The convective-resolving solutions adopting Large Eddy Simulation (LES) turbulent closure converge with respect to the overall flow field structure when grid spacing is properly reduced. By comparing the rainfall fields produced by the model on larger scales with those at the convergence scales it's possible to size up the uncertainty introduced by the modelling itself on the predicted ground effects in such simplified scenario

Validation of computational approaches for antiretroviral dose optimization

Strategies for reducing antiretroviral doses and drug costs can support global access, and numerous options are being investigated. Efavirenz pharmacokinetic simulation data generated with a bottom-up physiologically based model were successfully compared with data obtained from the ENCORE (Exercise and Nutritional Interventions for Cardiovascular Health) I clinical trial (efavirenz at 400 mg once per day versus 600 mg once per day). These findings represent a pivotal paradigm for the prediction of pharmacokinetics resulting from dose reductions. Validated computational models constitute a valuable resource for optimizing therapeutic options and predicting complex clinical scenarios

Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter

The SLC22A1 influx transporter is expressed on the basolateral membrane of hepatocytes and is involved in the excretion of numerous cations. Inhibition of SLC22A1 by several antiretrovirals, such as the protease inhibitor darunavir, has not previously been determined. In order to better understand and predict drug-SLC22A1 interactions, a range of antiretrovirals were screened for SLC22A1-associated inhibition and transport. Stable SLC22A1-expressing KCL22 cells were produced previously by nucleofection. Control KCL22 cells were transfected with the empty vector pcDNA3.1. Accumulation of tetraethylammonium (5.5 μM, 30 min) was determined in SLC22A1-expressing and mock-transfected cells with and without 50 μM of SLC22A1 inhibitor prazosin, or 50 μM of each antiretroviral drug. SLC22A1 IC50 values for efavirenz, darunavir, and prazosin were determined. Cellular accumulation of efavirenz and darunavir was also assessed in SLC22A1-expressing KCL22 cells and reversibility of this accumulation was assessed using prazosin. Tetraethylammonium accumulation was higher in SLC22A1-expressing cells compared to mock-transfected cells (10.6 ± 0.8 μM vs. 0.3 ± 0.004 μM, p = 0.009) and was significantly reduced in SLC22A1-expressing cells when co-incubated with all antiretrovirals tested except atazanavir, lamivudine, tenofovir, zidovudine, and raltegravir. Particularly noticeable was the predominance of SLC22A1 inhibitors in the protease inhibitor and non-nucleoside reverse transcriptase inhibitor classes. Absolute SLC22A1 IC50 values for efavirenz, darunavir, and prazosin were 21.8, 46.2, and 2.8 μM, respectively. Efavirenz accumulation was higher in SLC22A1-expressing cells compared to mock-transfected cells (17% higher, p = 0.009) which was reversed using prazosin, whereas no difference was observed for darunavir (p = 0.86). These data inform the mechanistic basis for disposition, drug-drug interactions and pharmacogenetic candidate gene selection for antiretroviral drugs

Logical gates in actin monomer

© 2017 The Author(s). We evaluate information processing capacity of a single actin molecule by calculating distributions of logical gates implemented by the molecule via propagating patterns of excitation. We represent a filamentous actin molecule as an excitable automaton network (F-actin automaton). where every atom updates its state depending on states of atoms its connected to with chemical bonds (hard neighbours) and atoms being in physical proximity to the atom (soft neighbours). A resting atom excites if a sum of its excited hard neighbours and a weighted sum of its soft neighbours belong to some specified interval. We demonstrate that F-actin automata implement OR, AND, XOR and AND-NOT gates via interacting patterns of excitation. Gate AND is the most common gate and gate XOR is the rarest. Using the architectures of gates discovered we implement one bit half-adder and controlled-not circuits in the F-actin automata. Speed and space values of the F-actin molecular computers are discussed

Assessing uncertainty in radar measurements on simplified meteorological scenarios

A three-dimensional radar simulator model (RSM) developed by Haase (1998) is coupled with the nonhydrostatic mesoscale weather forecast model Lokal-Modell (LM). The radar simulator is able to model reflectivity measurements by using the following meteorological fields, generated by Lokal Modell, as inputs: temperature, pressure, water vapour content, cloud water content, cloud ice content, rain sedimentation flux and snow sedimentation flux. This work focuses on the assessment of some uncertainty sources associated with radar measurements: </p><ol> <li>absorption by the atmospheric gases, e.g., molecular oxygen, water vapour, and nitrogen; </li> <li>attenuation due to the presence of a highly reflecting structure between the radar and a &quot;target structure&quot;. </li> </ol> RSM results for a simplified meteorological scenario, consisting of a humid updraft on a flat surface and four cells placed around it, are presented

A recombination test to classify mutants of Bacillus subtilis of identical phenotype

SUMMARYWe have developed a recombination test inBacillus subtilisthat provides a tool for rapid genetic classification of mutants of identical phenotype. The test has been used to classify 25 ts mutants in nine recombination classes that have been proved by independent evidence to correspond to nine genetic loci